Novel gene-specific translation mechanism of dysregulated, chronic inflammation reveals promising, multifaceted COVID-19 therapeutics

Wang, Li; Muneer, Adil; Xie, Ling; Zhang, Feng; Wu, Bing; Liu, Mei; Lenarcic, Erik M.; Feng, Emerald Hillary; Song, Juan; Xiong, Yan; Yu, Xufen; Wang, Charles; Gheorghe, Ciprian P.; Torralba, Karina D.; Cook, Jeanette Gowen; Wan, Yisong Y.; Moorman, Nathaniel J.; Song, Hongjun; Jin, Jian; Chen, Xian

doi:10.1101/2020.11.14.382416

Cited by 16 publications

(10 citation statements)

References 76 publications

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“…In SARS-CoV-2, trans-nasal and trans-synaptic mechanisms might allow the virus to invade the olfactory bulb and brainstem, with both being the possible initial site for CNS invasion [ 179 ]. Once the virus enters the CNS, it affects neurons, microglia, oligodendrocytes, and especially astrocytes, undermining neurons viability [ 17 , 179 , 180 ].…”

Section: Coronaviruses and Covid-19mentioning

confidence: 99%

Cognitive decline following acute viral infections: literature review and projections for post-COVID-19

Damiano

Guedes

Rocca

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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Recently, much attention has been drawn to the importance of the impact of infectious disease on human cognition. Several theories have been proposed, to explain the cognitive decline following an infection as well as to understand better the pathogenesis of human dementia, especially Alzheimer’s disease. This article aims to review the state of the art regarding the knowledge about the impact of acute viral infections on human cognition, laying a foundation to explore the possible cognitive decline followed coronavirus disease 2019 (COVID-19). To reach this goal, we conducted a narrative review systematizing six acute viral infections as well as the current knowledge about COVID-19 and its impact on human cognition. Recent findings suggest probable short- and long-term COVID-19 impacts in cognition, even in asymptomatic individuals, which could be accounted for by direct and indirect pathways to brain dysfunction. Understanding this scenario might help clinicians and health leaders to deal better with a wave of neuropsychiatric issues that may arise following COVID-19 pandemic as well as with other acute viral infections, to alleviate the cognitive sequelae of these infections around the world.

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Section: Coronaviruses and Covid-19mentioning

confidence: 99%

Cognitive decline following acute viral infections: literature review and projections for post-COVID-19

Damiano

Guedes

Rocca

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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“…The number of neutrophils, macrophages, and lymphocytes were lowered clearly, and the levels of IL-1β, IL-6, and TNF-α in the BALF were decreased, while IL-10 was elevated. Epigenetic changes are linked to lymphocyte movement, as G9a depletion blocks T-cell migration (32), and inhibition of G9a-associated pathways produced systematic mitigation of inflammation and suppression of viral replication (33). These results suggest G9a knockdown repressed inflammation in Spn mice.…”

Section: Discussionmentioning

confidence: 89%

G9a promotes inflammation in Streptococcus pneumoniae induced pneumonia mice by stimulating M1 macrophage polarization and H3K9me2 methylation in FOXP1 promoter region

Li¹,

Li²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Streptococcus pneumoniae has become a leading cause of pneumonia in recent years. Here, we investigated the mechanism of histone methylase G9a in Streptococcus pneumoniae-induced pneumonia (Spn).Methods: G9a expression in Spn mouse tissue was measured. G9a lentivirus interference vector was injected into Spn mice to evaluate the wet and dry weight of the right upper lobe and the total lung water content (TLW) and wet/dry ratio (W/D). The number of neutrophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid (BALF) was detected, and the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and IL-10 in BALF were assessed. The expressions of M1 and M2 macrophage markers were also detected. The enrichment of histone 3 lysine 9 dimethylation (H3K9me2) in the Forkhead Box P1 (FOXP1) promoter was detected by chromatin immunoprecipitation (ChIP) assay, and the transcription level of FOXP1 was detected. Mouse macrophage RAW264.7 was induced by lipopolysaccharide (LPS) following G9a interference.Results: G9a in the lung tissue of Spn mice was increased. After G9a knockdown, the mouse weight increased, the infiltration of inflammatory cells was decreased, levels of pro-inflammatory cytokines in BALF were decreased, CD86 and inducible nitric oxide synthase (iNOS) were decreased, and CD206 and arginase-1 (Arg-1) were elevated. In LPS-induced RAW264.7, G9a inhibited macrophage polarization to M1 and promoted macrophage polarization to M2. G9a promoted H3K9me2 methylation in the FOXP1 promoter region and inhibited its transcription, while FOXP1 downregulation reversed the inhibition of G9a knockdown on macrophage polarization to M1 and the inflammatory effect on Spn mice.Conclusions: G9a promotes M1 polarization of macrophages by promoting H3K9me2 methylation in the FOXP1 promoter region, promoting an inflammatory response in Spn mice.

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“…Eric Song et.al. found that in the cerebrospinal fluid (CSF) of COVID-19 patients, these activated innate immune cell populations are predicted to interact with CD8 and CD4 T cells applicating CellPhoneDB, suggesting a coordinated anti-viral immunological response occurring in the CSF of COVID-19 patients [ 72 ].…”

Section: Analytical Tools For Ligand-receptor Interactions At Single-cell Levelmentioning

confidence: 99%

Applications and analytical tools of cell communication based on ligand-receptor interactions at single cell level

Zhang

Song

et al. 2021

Cell Biosci

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Background Cellular communication is an essential feature of multicellular organisms. Binding of ligands to their homologous receptors, which activate specific cell signaling pathways, is a basic type of cellular communication and intimately linked to many degeneration processes leading to diseases. Main body This study reviewed the history of ligand-receptor and presents the databases which store ligand-receptor pairs. The recently applications and research tools of ligand-receptor interactions for cell communication at single cell level by using single cell RNA sequencing have been sorted out. Conclusion The summary of the advantages and disadvantages of analysis tools will greatly help researchers analyze cell communication at the single cell level. Learning cell communication based on ligand-receptor interactions by single cell RNA sequencing gives way to developing new target drugs and personalizing treatment.

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Novel gene-specific translation mechanism of dysregulated, chronic inflammation reveals promising, multifaceted COVID-19 therapeutics

Cited by 16 publications

References 76 publications

Cognitive decline following acute viral infections: literature review and projections for post-COVID-19

Cognitive decline following acute viral infections: literature review and projections for post-COVID-19

G9a promotes inflammation in Streptococcus pneumoniae induced pneumonia mice by stimulating M1 macrophage polarization and H3K9me2 methylation in FOXP1 promoter region

Applications and analytical tools of cell communication based on ligand-receptor interactions at single cell level

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